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Trial registered on ANZCTR

Registration number

ACTRN12618001114235

Ethics application status

Approved

Date submitted

28/06/2018

Date registered

5/07/2018

Date last updated

10/09/2023

Date data sharing statement initially provided

10/09/2023

Date results provided

10/09/2023

Type of registration

Retrospectively registered

Titles & IDs

Public title

Development of Risk Models for Cognitive Decline and Delirium in Patients Undergoing Transcatheter Aortic Valve Implantation (TAVI)

Scientific title

Development of Risk Models for Cognitive Decline and Delirium in Aortic Stenosis and Transcatheter Aortic Valve Implantation (TAVI)

Secondary ID [1]

nil known

Universal Trial Number (UTN)

U1111-1213-6749

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Aortic stenosis

Delirium

Cognitive decline

Condition category

Condition code

Cardiovascular

Diseases of the vasculature and circulation including the lymphatic system

Mental Health

Other mental health disorders

Surgery

Other surgery

Intervention/exposure

Study type

Observational

Patient registry

False

Target follow-up duration

Target follow-up type

Description of intervention(s) / exposure

This study will identify possible risk factors for delirium (for two days post-procedurally) and cognitive decline (at 3-, 6- and 12-months post-procedurally) in older adults undergoing transcatheter aortic valve implantation. Possible risk factors include medical history, procedural variables and a range of baseline assessments (non-invasive brain imaging (EEG), APOE-e4 genotype from a saliva sample, and symptoms of frontostriatal dysfunction (gait characteristics, visual symptoms, voice assessment, and a range of questionnaires regarding swallowing, depression, anxiety, sleep disturbance and changes to behaviour).
Participants will be required to complete a baseline assessment of 90 minutes duration, with the additional option of participating in the collection of resting EEG. The baseline assessment consists of questions about education, social and physical activity history, the Edmonton Frail Scale, The Addenbrooke's Cognitive Examination, CANTAB (The motor screening test, reaction time test and pattern recognition test), the Geriatric Depression Scale, insomnia items from the Hamilton Rating Scale for Depression, 6m gait task, dual 6m cognition/gait task, visual acuity, diplopia assessment, measuring of blink rate, one question from the Sydney Swallowing Questionnaire, three 5 second phonations of the vowel "ah" analysed using the iPad voice analyst app, the Neuropsychiatric Questionnaire, Euroqol-5D, and the Barthel Index (Modified).
For two days following the TAVI procedure, participants will be assessed for delirium and delirium severity for a duration of 20 minutes using the Confusion Assessment Method and Memorial Delirium Assessment Scale. Follow-up of 60 minutes in duration will be completed at 3-, 6- and 12- months consisting of the Addenbrooke's Cognitive Examination, CANTAB (The motor screening test, reaction time test and pattern recognition test)Euroqol-5D, and the Barthel Index (Modified).

Intervention code [1]

Not applicable

Comparator / control treatment

The control group will be age-matched participants screened and not found to have heart murmur (i.e. non severe aortic stenosis participants). The rate of cognitive decline of the TAVI participants will be calculated based on the changes of the control group over the same time-frame.
The baseline assessment consists of questions about education, social and physical activity history, the Edmonton Frail Scale, The Addenbrooke's Cognitive Examination, CANTAB (The motor screening test, reaction time test and pattern recognition test), the Geriatric Depression Scale, insomnia items from the Hamilton Rating Scale for Depression, 6m gait task, dual 6m cognition/gait task, visual acuity, diplopia assessment, measuring of blink rate, one question from the Sydney Swallowing Questionnaire, three 5 second phonations of the vowel "ah" analysed using the iPad voice analyst app, the Neuropsychiatric Questionnaire, Euroqol-5D, and the Barthel Index (Modified).
Follow-up of 60 minutes in duration will be completed at 3-, 6- and 12- months consisting of the Addenbrooke's Cognitive Examination, CANTAB (The motor screening test, reaction time test and pattern recognition test)Euroqol-5D, and the Barthel Index (Modified).

Control group

Active

Outcomes

Primary outcome [1]

Delirium assessed using the Confusion Assessment Method and the Confusion Assessment Method-ICU

Timepoint [1]

one and two days post TAVI

Primary outcome [2]

Cognitive decline measured using the Addenbrooke's Cognitive Examination and the Cambridge Neuropsychological Test Automated Battery

Timepoint [2]

3-, 6- and 12- months post TAVI

Secondary outcome [1]

Hospital acquired complications documented in the medical records as per the Australian Commission on Safety and Quality in Healthcare.
https://www.safetyandquality.gov.au/our-work/indicators/hospital-acquired-complications/

Timepoint [1]

30 days

Secondary outcome [2]

Quality of life measured using the EuroQol

Timepoint [2]

3-, 6- and 12- months post TAVI.

Secondary outcome [3]

Delirium severity using the Memorial Delirium Assessment Scale

Timepoint [3]

one and two days post TAVI

Secondary outcome [4]

Delirium subtype using Meagher's descriptions (2009).

Timepoint [4]

one and two days post TAVI

Secondary outcome [5]

mortality

Timepoint [5]

3-, 6- and 12- months post TAVI.

Secondary outcome [6]

functional activity measured using the Barthel (modified) Index

Timepoint [6]

3-, 6- and 12- months post TAVI

Eligibility

Key inclusion criteria

Inclusion criteria for the TAVI group include undergoing elective TAVI at the Royal Adelaide Hospital, male or female, and aged over 60 years. Participants with a clinical diagnosis of a neurodegenerative condition (including dementia) will be eligible for inclusion as it is reflective of the general older population who would be considered appropriate for cardiovascular procedures and thus will facilitate clinical translation of study results (note: different consent process for those with a clinical diagnosis of dementia).
Inclusion criteria for the control group include male or female, and aged over 60 years. Participants with a clinical diagnosis of a neurodegenerative condition including dementia will be eligible for inclusion (note: different consent process for those with a clinical diagnosis of dementia).

Minimum age

60 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Yes

Key exclusion criteria

Key exclusion criteria include current or recent (within the past year) alcohol or substance abuse or dependence, use of recreational drugs (within the past month), a diagnosed learning disability, insufficient English language, hearing (with aids) or vision (with glasses) to complete assessment tasks.
Control participants will be excluded if they are found to have a heart murmur and/or aortic stenosis, a history of cardiovascular disease.
TAVI participants will be excluded if they are already enrolled in a TAVI clinical trial.

Study design

Purpose

Screening

Duration

Longitudinal

Selection

Convenience sample

Timing

Prospective

Statistical methods / analysis

A base model for delirium after TAVI (using apical implantation approach, female gender, age, atrial fibrillation, creatinine, carotid disease and stroke/transient ischemic attack) had a receiver operatic characteristic (ROC) curve c-statistic of 0.79. Further research is still required as the results may have reduced generalizability given other studies have found these risk factors not to be associated with delirium. Thus, utilising G* power statistical analysis software, a priori sample size was calculated using an equivalent effect side of f2 =0.325. With f2 =0.325, power=0.95 and a=0.05, the computed sufficient sample size is n= 36 (per group). A recruitment strategy of 100 participants per group will ensure the study is sufficiently powered not only for the detection of presence vs absence of delirium, but also the assessment of delirium severity (requiring greater numbers); especially given the ambiguity for these risk factors found in other studies and risk of drop-out and death across the study period.

Data will be entered into Excel and SPSS for analysis. EEG data will be processed using software such as MATLAB, MATLAB toolboxes, ERPlab and EEGlab. Recruitment of 100 participants for each group is sufficient to ensure the study is adequately powered. The statistical methods that will be used to identify risk factors and develop risk models will include logistic regression, ridge regression and lasso. Cross-validation will be used to determine which statistical model minimises over-fitting or under-fitting. Standard multivariate regression assumptions will be examined including multivariate outliers, multicollinearity, normality of residuals and influential cases. In determining the differences between TAVI participants and control participants for cognition, mood, behaviour, sleep and motor characteristics, the appropriate parametric (e.g. t-test) or non-parametric test (e.g. Mann Whitney, Fisher-Exact test) will be selected. Multiple comparisons will be controlled for using the Holm Method. Only group-level de-identified data will be presented.

Recruitment

Recruitment status

Stopped early

Data analysis

Data analysis is complete

Reason for early stopping/withdrawal

Lack of funding/staff/facilities

Date of first participant enrolment

Anticipated

Actual

1/05/2018

Date of last participant enrolment

Anticipated

1/11/2019

Actual

31/05/2021

Date of last data collection

Anticipated

1/11/2020

Actual

31/05/2022

Sample size

Target

200

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

Recruitment hospital [1]

The Royal Adelaide Hospital - Adelaide

Recruitment postcode(s) [1]

5000 - Adelaide

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

Research Training Program Scholarship, Department of Education and Training, Australian Government.

Address [1]

Department of Education and Training
GPO Box 9880
Canberra ACT 2601

Country [1]

Australia

Primary sponsor type

University

Name

University of South Australia

Address

Prof Hannah Keage
Cognitive Ageing and Impairment Neurosciences
School of Psychology, Social Work and Social Policy
Adelaide
South Australia 5000

GPO Box 2471
Adelaide
South Australia 5001
Australia

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Central Adelaide Local Health Network Human Research Ethics Committee (CALHN HREC)

Ethics committee address [1]

CALHN Research Office
L3 Roma Mitchell House, North Terrace, Adelaide, SA 5000.

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

21/09/2017

Approval date [1]

13/12/2017

Ethics approval number [1]

R20170916

Summary

Brief summary

This study aims to identify risk factors for a deterioration in thinking and memory skills after a type of heart procedure known as transcatheter aortic valve implantation (TAVI). These changes may be short-term (such as delirium) or long-term cognitive decline. There will be 100 participants undergoing TAVI and 100 age-matched controls.
Another part of this study will compare the 100 participants undergoing TAVI and the 100 control participants before the TAVI procedure i.e. the baseline data. This analysis will identify if participants with aortic stenosis compared with participants without aortic stenosis have different motor symptoms (walking, eye movement, voice, swallowing), mood, behaviour, brain activity (measured non-invasively using electroencephalogram or EEG), and their genotype taken from a saliva sample (with consent from participants).

Trial website

Trial related presentations / publications

Public notes

Protocol paper - DOI: 10.3389/fcvm.2021.657057/
Outcomes paper - DOI:10.56392/001c.74542

Attachments [1]

/AnzctrAttachments/375058-Delirium TAVR study Ethics Approval.pdf (Ethics approval)

Attachments [2]

/AnzctrAttachments/375058-Ethics ammendment approval.docx (Ethics approval)

Attachments [3]

/AnzctrAttachments/375058-1-TAVI consent form for self.doc (Participant information/consent)

Attachments [4]

/AnzctrAttachments/375058-2-TAVI consent form for person responsible ET.doc

Attachments [5]

/AnzctrAttachments/375058-3- Control consent form for self ET.doc (Participant information/consent)

Attachments [6]

/AnzctrAttachments/375058-4- Control consent form for person responsible ET.doc (Participant information/consent)

Attachments [7]

/AnzctrAttachments/375058-5-Family member control consent form for self ET.doc (Participant information/consent)

Attachments [8]

/AnzctrAttachments/375058-6-Family member TAVI consent form for self ET.doc (Participant information/consent)

Attachments [9]

/AnzctrAttachments/375058-TAVI Study - Erica Tilley - Assessment Booklet 15 May.docx (Other)

Contacts

Principal investigator

Name

Prof Hannah Keage

Address

Cognitive Ageing and Impairment Neurosciences
School of Psychology, Social Work and Social Policy
University of South Australia
Adelaide
South Australia 5000
GPO Box 2471
Adelaide
South Australia 5001
Australia

Country

Australia

Phone

+61 8 83024340

Fax

[email protected]

Contact person for public queries

Name

Hannah Keage

Address

Country

Australia

Phone

+61 8 83024340

Fax

[email protected]

Contact person for scientific queries

Name

Hannah Keage

Address

Country

Australia

Phone

+61 8 83024340

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

Yes

What data in particular will be shared?

Data underlying primary outcomes only.
Please see https://data.unisa.edu.au/dap/Project.aspx?ProjectID=742756

When will data be available (start and end dates)?

Data is currently available with no end date determined.
Please see https://data.unisa.edu.au/dap/Project.aspx?ProjectID=742756

Available to whom?

Any member of the public has access via the below link.
Please see https://data.unisa.edu.au/dap/Project.aspx?ProjectID=742756

Available for what types of analyses?

Any purpose.
Please see https://data.unisa.edu.au/dap/Project.aspx?ProjectID=742756

How or where can data be obtained?

https://data.unisa.edu.au/dap/Project.aspx?ProjectID=742756

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
20297	Data dictionary		https://data.unisa.edu.au/dap/Project.aspx?ProjectID=742756	[email protected]

Results publications and other study-related documents

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No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

Trial Review

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